tbuckley/cabot-search huggingface dataset:
Systematic review and meta-analysis of the accuracy and applicability of blood-based multi-cancer early detection (MCED) in the general population.
Authors: Joo Hee Park, Youjin Oh, Liam Il-Young Chung, Richard Duan, Trie Arni Djunadi, Sung Mi Yoon, Zunairah Shah, Chan Mi Jung, Ilene Hong, Leeseul Kim, Young Kwang Chae
Journal: Journal of Clinical Oncology (2023)

3069 Background: Globally, cancer results in 10.08 million deaths per year. A single blood-based screening tool that detects multiple cancer types could significantly reduce cancer burden. We systematically reviewed and statistically examined both the accuracy and applicability of blood-based MCED tests to strategize their utilization in improving cancer detection. Methods: Original articles were searched from PubMed, Cochrane, and Embase for blood-based screening tests analyzing multiple cancer types and asymptomatic human subjects. We excluded studies with small sample sizes (n&lt;30), hypothesis-generating/diagnostic tests, and non-blood-based tests. For cfDNA-based assays, measurements of diagnostic accuracy were pooled for meta-analysis. Results: Of 1,074 records identified and screened, 15 case-control and 4 cohort studies were analyzed, most of which utilized cfDNA-based diagnostic tests. Twelve cfDNA studies selected for meta-analysis had pooled sensitivity of 0.623 (95%CI 0.517 - 0.719) and specificity of 0.975 (0.942 - 0.990). Summary ROC curve shows variability in sensitivity and specificity between studies. However, sensitivity and specificity were not affected by study type, gender, or assay type. Sensitivity was higher for advanced staged cancers (III/IV 0.774 (0.697 - 0.837)) than early-stage cancers (I/II 0.503 (0.366 - 0.639)). Among cancer types, no significant differences were detected. Lastly, false positive and false negative rates were 0.025 (0.010 - 0.058) and 0.447 (0.438 - 0.456), respectively. Conclusions: Given high sensitivities and specificities, MCED tests show promise as additional screening tools. However, in the general population, misdiagnosis burden from false positive and negative rates is anticipated. Although multiple barriers exist to their application in the clinic, MCED tests may improve patient outcomes for cancers with no conventional screening tools and provide additional credibility when combined with existing tools. Future prospective studies with large and diverse populations are warranted. [Table: see text]
ScRNA-seq to examine heterogeneity of transcriptional regulation of CAFs between left-sided and right-sided CRC.
Authors: Tongqiang Fan, Qian Wang, Tao Wang, Shanshan Xiao
Journal: Journal of Clinical Oncology (2023)

e15548 Background: Cancer-associated fibroblasts (CAFs) play prominent and diverse tumor-promoting function roles in tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation between left-sided and right-sided CRC (colorectal cancer). Methods: We collected a public scRNA-seq dataset (Pelka et al., 2021) with 21 samples from left-sided CRC and 79 from right-sided CRC. Only CAFs were extracted for downstream analysis. Seurat (Stuart et al., 2019), Monocle2 (den Berge et al., 2020) and pySCENIC (Aibar et al., 2017) were used to perform dimensionality reductions, differential analysis, pseudo-time trajectory analysis, and the transcriptional regulation analysis, respectively. Results: Firstly, we performed differential analysis on 2,049 cells from 62 of 100 samples that contained CAFs. The results showed that highly expressed genes including IGFBP1, IGFBP2, LCN2, ALDH1A1 and CASP1 in left-sided CRC were mainly enriched in immune response pathway, while up-regulated genes in right-sided CRC were neutrophil-migration-chemotaxis-related such as PPBP1, PF4V1, CCL7, CXCL3 and CXCL8. Then, we classified 2,049 CAFs into four subclusters based on the markers of CCL8 + CAF, CXCL14 + CAF, GREM1 + CAF and MMP3 + CAF. The proportion of CXCL14 + CAF was higher in left-sided CRC while MMP3 + CAF was preferentially enriched in right-sided CRC, which was also independently validated by 33 TCGA cohorts. Further investigation on those subclusters showed that CXCL14 + CAF was myCAF, while the rest (CCL8 + CAF, MMP3 + CAF and GREM1 + CAF) were iCAF. After investigating the heterogeneity of CAFs, we focused on the transcriptional regulatory networks (TRNs). The results showed that the dominant regulons in left-sided CRC ( HOXD9, HSF2, MYBL1, HES6, XRCC4, and ZNF585B) and right-sided CRC ( CREB5, ZNF274, IRF7, TFEC, NR2F1, and PITX3) were distinct, which highlighted the heterogeneity and plasticity of CAF-based TRNs between left-sided and right-sided CRC. Conclusions: Collectively, although further experimental verification is required to establish the functional roles of each CAF cluster and the diverse origins of CAFs, this study may facilitate better understanding molecular mechanism of CAF-targeted therapy strategies in CRC.
A phase 1, open-label, first-in-human study of TAS2940 in patients with advanced solid tumors.
Authors: Jordi Rodon Ahnert, David R. Spigel, Jill Kremer, Leah Jin, Karim Adnane Benhadji, Maciej Gil, Benjamin Besse
Journal: Journal of Clinical Oncology (2023)

TPS3165 Background: Aberrant expression and signaling of the ERBB family of receptor tyrosine kinases, including epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), has a role in the pathogenesis of solid tumors such as breast cancer (BC), non–small cell lung cancer (NSCLC), and glioblastoma (GBM). Although therapies that target HER2 are effective in early and advanced HER2-overexpressing BC, many patients develop resistance despite tumor dependence on HER2 at the time of progression. Approximately 4% of patients with NSCLC have HER2 mutations, mostly presenting as exon 20 insertions (ex20ins); however, approved HER2/EGFR tyrosine kinase inhibitors (TKIs) have limited efficacy in patients with NSCLC and HER2 ex20ins. Many patients with NSCLC or BC develop brain metastases, and EGFR alterations, including EGFRvIII mutations, are common in GBM. There is therefore a need for a brain-penetrable TKI with activity against tumors harboring HER2/EGFR alterations. TAS2940 is a potent, selective, and orally bioavailable pan-ERBB inhibitor that has shown promising preclinical efficacy against cancers with a variety of HER2/EGFR mutations and amplifications. Further, TAS2940 inhibited tumor growth and induced tumor regression in a dose-dependent manner in nude mice intracranially implanted with NCI-N87, a HER2-overexpressing human gastric cancer cell line. Methods: TAS2940-101 (NCT04982926) is an open-label, phase 1, first-in-human trial to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of TAS2940 in patients with advanced solid tumors and HER2/ EGFR aberrations. Eligible patients are aged ≥18 years, have non-measurable (Part 1) or measurable (Part 1 and 2) disease per RECIST 1.1 or RANO criteria, ECOG performance status 0/1, and adequate organ function. Patients with non-stable brain metastases are excluded. Part 1 (dose escalation) will use a Bayesian optimal interval design with a starting dose of 15 mg/kg orally QD (planned dose levels: 15, 30, 60, 120, 240 and 480 mg). Once the recommended phase 2 dose is determined, Part 2 (dose expansion) will enroll patients with NSCLC (Cohort A), HER2+ BC (Cohort B), recurrent/refractory GBM (Cohort C), or other solid tumors with EGFR/ HER2 aberrations (Cohort D). The primary objectives are the maximum tolerated dose of TAS2940 in Part 1 and antitumor activity in Part 2. Secondary objectives include antitumor activity in Part 1. The safety and PK profile of TAS2940 will be assessed in both parts. Approximately 142 patients will be enrolled, comprising ~42 in Part 1 and ~100 in Part 2. As of January 24, 2023, 15 patients have been enrolled. No dose-limiting toxicities have been reported with dose escalation up to 240 mg QD. Recruitment is ongoing. Clinical trial information: NCT04982926 .
Trends and disparities in incidence and mortality of early-onset colorectal cancer (EOCRC) in the United States (1999-2019).
Authors: Udhayvir Singh Grewal, Davendra Sohal
Journal: Journal of Clinical Oncology (2023)

e15551 Background: There has been a startling rise in the reported incidence of colorectal cancer (CRC) among adolescents and young adults (AYA; ages 15-39 years) in the US.These patients are often diagnosed with advanced stage and have a relatively poor prognosis.Population-based data on disparities and trends in incidence and mortality in this understudied population are lacking. Methods: We used the Centers for Disease Control WONDER cancer statistics database to extract data on annual age-adjusted incidence (AAIR) and mortality (AAMR) rates per 100,000 population for colon and rectal cancer in AYA. We compared AYA statistics with the overall as well as the non-AYA population (40-85 years). Sex and race comparisons were analyzed. Variations in AAIR and AAMR over time, assessed with Joinpoint regression modelling (Joinpoint regression program 4.9.1.0), were expressed as estimated average annual percentage change (AAPC). Comparisons were reported using average annual percentage change difference (AAPCD). Results: 83,371 cases of EOCRC were reported between 1999-2019. We recorded an increase in AAIR of EOCRC (AAPC 2.9, p &lt; 0.001). We noted a concomitant decline in AAIR of CRC overall (AAPC -2.4, P &lt; 0.001) and among the non-AYA population (AAPC -2.4, p &lt; 0.001). Subgroup comparisons showed statistically significant differences in AAIR of EOCRC for females vs males (AAPCD 0.6, p = 0.04), Whites vs Blacks (AAPCD 1.8, p &lt; 0.001), and White females vs White males (AAPCD 0.6, p = 0.02) [table]. AAMR increased for EOCRC over the study period (AAPC 0.8, p = 0.001), as opposed to a decline in AAMR of CRC overall (AAPC -2.5, p &lt; 0.001) and among the non-AYA population (AAPC -2.5, p &lt; 0.001). The increase in AAMR of EOCRC was similar among males and females (AAPCD 0.3, p = 0.351), but higher among Whites vs Blacks (AAPCD 1.1, p = 0.007). Conclusions: This analysis from a large population-level database shows an increasing trend in incidence and mortality of EOCRC in the US, despite a concomitant decline in the incidence and mortality of CRC overall. The incidence appears to be rising more rapidly among females, particularly White females. Both incidence and mortality of EOCRC appear to be rising more rapidly among Whites compared with Blacks. Our analysis underscores the critical need to develop strategies to identify high-risk AYA populations who may benefit from more aggressive CRC screening and prevention interventions. [Table: see text]
Outcomes of early onset colorectal cancer (EOCRC) with synchronous liver oligometastasis.
Authors: Oluwadunni Eunice Emiloju, Mohamed Elboraey, Seyed Ali Montazeri, Karim Zaazoue, Jeremy Clifton Jones, Christina Wu, Beau Toskich, Joleen M. Hubbard
Journal: Journal of Clinical Oncology (2023)

e15599 Background: Screening and removal of pre-malignant adenomas has reduced CRC incidence in adults older than 50 years (later onset CRC [LOCRC]), but EOCRC incidence has increased by 1-2% annually since the 1990s. The liver is the commonest site of CRC metastasis, and EOCRC presents with more advanced stage compared with LOCRC. Oligometastasis (OM) refers to potentially resectable CRC, and complete resection of CRC primary and OM is associated with improved survival and potential cure. Here, we examined treatment outcomes of EOCRC with synchronous liver oligometastases (sLiOM) at our institution. Methods: We performed a retrospective review of institutional electronic health records and identified 160 EOCRC patients with sLiOM treated with curative intent in the last decade. Demographics, treatment, and follow up data were recorded, and analysis for survival outcomes performed. The study protocol was exempt after review by Mayo Clinic institutional review board. Results: Of 160 patients, median age at diagnosis was 43 years. Primary tumor was in the left colorectum in 73% and right colon in 26% of patients. Metastasis was limited to the liver only in 64%, and liver metastasis was solitary in 14% of patients (table 1). Fluoropyrimidine doublet backbone (81%) was more commonly used compared to triplet (19%), with doublet + bevacizumab (41%) as the most common regimen. Hepatectomy only (59%), combined hepatectomy with ablation (32%), ablation only (5%), transarterial radioembolization (2%), and trans arterial embolization (1%) were the modalities employed for sLiOM. Of the 148 patients who underwent hepatectomy, R0 resection was achieved in 51%. After a median follow-up of 37 months, progression-free survival was 11.6 mos (95% CI 9-14mos) and median overall was 83.6 mos (95% CI 62-105mos). The median time to liver progression was 16 mos (95% CI 12-20 mos). At data cut off, 41 patients (26%) were alive and disease-free, and 60 patients (38%) were alive and disease free in the liver only. Conclusions: This multi-site, retrospective analysis of EOCRC patients demonstrates excellent survival outcomes with localized treatment of sLiOM. Median OS in this cohort compares favorably to previously reported mOS of 36 months in EOCRC patients (Arhin et al, 2021). Cure is not often achieved even after treatment of sLiOM in this cohort, suggesting aggressive disease biology and the need for improved patient selection. [Table: see text]
Effectiveness and safety of camrelizumab in advanced esophageal cancer: A prospective multicenter observational cohort studies (ESCORT-RWS).
Authors: Zhihao Lu, Jun Zhao, Zhe Yang, Na Li, Junsheng Wang, Shuanghu Yuan, Yusheng Wang, Suyi Li, Fengming Ran, Yinghua Ji, Yanqiao Zhang, Chen Wang, Lixin Wan, Ming Wang, Liang Liang, Xiaofang Dai, Guanghui Cheng, Wei Li, Peng Zhen, Lin Shen
Journal: Journal of Clinical Oncology (2023)

4049 Background: Camrelizumab, an anti-programmed death 1 (PD-1) monoclonal antibody, has demonstrated survival benefits in patients with advanced or metastatic esophageal squamous cell carcinoma. However, the real-world effectiveness and safety of camrelizumab in patients with advanced esophageal cancer are largely unknown. Methods: In this prospective multicenter observational cohort study (NCT04616040), patients with advanced esophageal cancer who were scheduled to receive camrelizumab at the discretion of the physicians in charge were screened for inclusion. Clinical outcomes were treatment emergent adverse events (TEAEs), objective response rate (ORR), disease control rate (DCR), time to treatment discontinuation (TTD), progression free survival (PFS), and overall survival (OS). Results: Between Dec. 24, 2020 and Dec. 30, 2022, data were available for 624 patients (median age: 64.5 years; 74 [11.9%] aged ≥75 years; 515 [82.5%] men; 20 [3.2%] ECOG PS ≥2; 602 [96.5%] esophageal squamous cell carcinoma) from 42 institutions in China. All patients received at least one dose of camrelizumab-containing therapy, including 305 (48.9%) in the first-line, 238 (38.1%) in the second-line, and 81 (13.0%) in the third or later line settings. Most patients were treated with camrelizumab plus chemotherapy (487 [78.0%], primarily taxane and platinum-based chemotherapy in 284 [45.5%] patients), followed by camrelizumab plus antiangiogenic therapy (64 [10.3%]), camrelizumab monotherapy (46 [7.4%]), and camrelizumab plus antiangiogenic therapy and chemotherapy (27 [4.3%]). TEAEs occurred in 541 (86.7%) patients, most commonly anemia (41.2%), decreased white blood cell (38.5%), and decreased neutrophil count (28.5%). No new safety signals were noted. At the data cutoff (Dec. 30, 2022), 152 (24.4%) patients were still on treatment. The median follow-up estimated by the reverse Kaplan-Meier method and effectiveness outcomes are summarized in the Table. Conclusions: The real-world effectiveness and safety profiles of camrelizumab in advanced esophageal cancer patients are generally consistent with those observed in pivotal clinical trials. [Table: see text]
Atezolizumab plus bevacizumab combined with transarterial embolization plus hepatic arterial infusion-chemotherapy for unresectable hepatocellular carcinoma with a diameter larger than 8 cm: A retrospective study.
Authors: Wenbo Guo, Hongjie Cai, Song Chen, Zhiqiang Wu, Fan Wang, Ludan Chen, Shuangyan Tang, Wenquan Zhuang
Journal: Journal of Clinical Oncology (2023)

e14617 Background: The combination of atezolizumab and bevacizumab (Atezo-Bev) has become the standard first-line therapeutic regimen for patients with unresectable hepatocellular carcinoma (uHCC), while the therapeutic effect is limited in patients with high-risk characteristics (vp3/vp4 portal vein tumor thrombus or high tumor burden). Locoregional therapy plays an important role in minishing tumor burden and synergistic antitumor effect with systemic therapy, including transarterial embolization (TAE) and hepatic arterial infusion chemotherapy (HAIC). Herein, this study aimed to assess the efficacy and safety of atezolizumab and bevacizumab combined with TAE and HAIC in unresectable hepatocellular carcinoma with high tumor burden. Methods: This retrospective study reviewed the medical records of patients who had primary uHCC with high tumor burden (maximum nodule diameter &gt;8 cm) receiving Atezo-Bev plus TAE and HAIC from September 2019 to September 2022 in our medical center. HAIC involved oxaliplatin, fluorouracil and leucovorin (FOLFOX regimen). Progression-free survival (PFS), overall survival (OS), tumor response according to mRECIST, and treatment-related adverse events (AEs) were evaluated. Results: In total, 30 patients were included in this study with a median follow-up period of 11.4 months. Twelve patients (40%) died and all the remaining patients reached the end point of PFS at the cut-off follow-up time. The median PFS of the 30 evaluable patients was 6.8 months (95% CI, 2.6-11.1 months), and the survival rates at 3 months, 6 months, 9 months, and 12 months were 86.2%, 82.5%, 68.6%, and 60%, respectively, and the median OS was not estimated (NE). According to the mRECIST, the objective response rate (ORR) was 74.4% (95% CI, 59.3%-89.5%), and the disease control rate (DCR) was 93.3% (95%CI, 85.4%-98.6%) respectively. Extrahepatic metastasis was an independent risk factor associated with PFS.As for the safety, there was no treatment-related mortality throughout the study period. The most common AEs were fever (6.7%), and diarrhoea(6.7%), and grade 3/4 AEs occurred among 6 patients (20%). Conclusions: Atezo-Bev combined with TAE and HAIC may be safe and effective for uHCC patients with high tumor burden, while further prospectively clinical research is necessary to validate the efficacy and safety.
A new approach to reduce toxicity and improve quality of life in colon cancer patients receiving adjuvant chemotherapy.
Authors: Rashida Orlova, Anna Varankina, Alexandra Androsova, Natalia P. Belyak, Svetlana Kutukova
Journal: Journal of Clinical Oncology (2023)

e15649 Background: We investigated the possibility of using accompanying therapy with enterosorbent in CRC patients receiving adjuvant chemotherapy. Methods: 40 pts (62 years [54.0-68.5]) with CRC (II-III) after radical surgery were randomized in 2 groups (1:1). Patients in the group 1 received ACT (XELOX), patients in group 2 received XELOX and enterosorbent "Polysorb" 30 mg orally, daily from 16 to 20 days of the ACT cycle. Results: The use of an enterosorbent can significantly reduce the manifestations of gastrointestinal toxicity: vomiting (5.0% vs 35.0%; p = 0.018), diarrhoea (5.0% vs. 40.0%; p = 0.008), flatulence ( 25.0% vs 70.0%; p = 0.004), constipation (0 vs 20.0%; p = 0.035) and abdominal pain (15.0% vs 50.0%; p = 0.018). In group 2, already by the 2nd cycle, the median scores on the QLQ-C30 symptomatology scale amounted to 22.0 points [14.0-28.5] vs 29.9 points [23.0-33.0] in the control group (p = 0.0441). By the 3 cycle in group 2, the average score on the QLQ-C29 symptomatic scale was 13.0±5.2 points (95% CI 10.5-15.4) and was significantly lower than in the control group (18.0±7.8 points (95% CI 14.3-21.6); p = 0.0224). When assessing the general condition according to the results of the analysis of the QLQ-C30 questionnaire, in the control group of patients there was a significant decrease in the number of points already by the beginning of the 2nd cycle of ACT - before the start of cycle 2 of ACT(p = 0.0369) and cycle 4 of ACT (p = 0.0447). Score of EQ-5D in the control group, significant decreases before 2 (from 84.9±6.4 points (95% CI 81.9-87.9) to 80.5 [77.55-86, 5]) (p = 0.0477) and 3 cycle ACT (from 80.5 [77.55-86.5] to 77.0±4.7 (95% CI 74.7-79.2)) (p = 0.0170), as well as a decrease in patient satisfaction with their condition at the time of the start of the 4th cycle of ACT compared with the baseline visit from 84.9±6.4 points (95% CI 81.9-87.9) to 75.7 ±6.7 points (95% CI 72.3-79.0) (p = 0.0001). Conclusions: The use of an enterosorbent as an accompanying therapy in CRC patients receiving ACT can significantly reduce the manifestation of chemotherapy toxicity and improve the quality of life of patients.
Difference in management of patients with prostate cancer and spinal cord compression in teaching vs non-teaching hospitals in the United States.
Authors: Omid Yazdanpanah, Aditi Sharma, Arash Rezazadeh
Journal: Journal of Clinical Oncology (2023)

e17116 Background: Spinal Cord Compression (SCC) secondary to metastatic prostate cancer is a complication that can lead to irreversible loss of neurologic function. Many factors including age, comorbidities, severity of the compression, and neurological deficit can affect the treatment from conservative management to radiation and surgery. We aimed to study the difference in practice patterns and their outcomes in teaching hospitals (TH) vs non-teaching hospitals (NTH) in the United States. Methods: Utilizing the National Inpatient Sample Database (NIS), we conducted a retrospective cohort study on hospitalizations with prostate cancer and SCC between 2016 and 2020 across the US. Patients were divided into two groups of TH and NTH. Demographics, comorbidities, treatment modality, length of hospitalization, costs, and mortality were compared between the two groups. We also studied patients’ characteristics and outcomes in TH and NTH according to their treatment strategy. Results: We identified 11,380 metastatic prostate cancer patients with SCC admitted to the hospitals with a 7-day median length of stay. While 27.4% underwent surgical procedure and 11.5% received inpatient radiation, 61.2% were treated conservatively. The median cost of hospitalization was $21,922 in TH and $15,141 in NTH ( P&lt; 0.001). Although the median age and Charlson Comorbidity Index did not differ between two groups ( P =0.12 &amp; 0.66 respectively), patients in TH were more likely to receive intervention (either radiation or surgery) compared to NTH (Surgery: 28.2% in TH vs 23.0% in NTH; P &lt;0.01 &amp; Radiation: 12.1% in TH vs 8.2% in NTH; P &lt;0.01). Mortality rate was lower in TH than NTH (4.5% vs 7.9%; P &lt; 0.01). In both TH and NTH, patients with private insurance were more likely to undergo surgery (TH: Surgery 25.1% vs Radiation 18.8%; P&lt; 0.05 &amp; NTH: Surgery 27.0% vs 6.9% P&lt; 0.05). Among different races, black patients were more likely to receive radiation than surgery in TH (34.2% vs 26.8%; P &lt;0.05). With no difference in comorbidities between surgery and radiation group in TH ( P =0.16), all-cause mortality was higher for those who received radiation than for surgery (4.4% vs 1.9%; P &lt;0.05) . Conclusions: This study indicated that practice pattern for the management of SCC in prostate cancer is different in teaching and non-teaching hospitals. In addition to more surgery being performed in teaching hospitals, the mortality rate was also lower. There was an association between race and insurance type with different treatment modalities. We also revealed that all-cause mortality was higher with radiation therapy compared to surgery in teaching hospitals.